Proxy completion of EQ-5D in patients with dementia.

There are measurement difficulties associated with the assessment of health-related quality of life (HRQL) in older people with dementia. The use of proxies is a commonly employed approach to overcome such problems. The research reported in this paper sought to identify, specifically for the EuroQol EQ-5D HRQL instrument, whether construct validity is greater for 'family caregivers' or 'clinicians' as two alternative sources of proxy information for patients with a diagnosis of dementia. This involved the exploration of the strength of the associations between clinical measures of illness severity and EQ-5D data. The data appear to reveal a pattern suggesting that the viewpoint of the proxy (i.e., clinician or family caregiver) is important. The findings suggest that the data provided by clinicians (when compared to data from carers) had higher construct validity for the more observable dimensions of the EQ-5D instrument (i.e., 'mobility' and 'self-care'). Conversely, the data from family carers had higher construct validity for the less observable dimensions (i.e., 'usual activities' and 'anxiety/depression'). Previous research on proxy provision of HRQL data has tended to focus on trying to identify a single proxy. The results of this study suggest that using carefully matched sets of measures and assessment perspectives may produce more valid EQ-5D health state descriptions.

Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.

BACKGROUND: Cholinesterase inhibitors produce small improvements in cognitive and global assessments in Alzheimer's disease. We aimed to determine whether donepezil produces worthwhile improvements in disability, dependency, behavioural and psychological symptoms, carers' psychological wellbeing, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long? METHODS: 565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate. Primary endpoints were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome assessments were sought for all patients and analysed by logrank and multilevel models. FINDINGS: Cognition averaged 0.8 MMSE (mini-mental state examination) points better (95% CI 0.5-1.2; p<0.0001) and functionality 1.0 BADLS points better (0.5-1.6; p<0.0001) with donepezil over the first 2 years. No significant benefits were seen with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; p=0.4) or progression of disability (58% vs 59% at 3 years; p=0.4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0.97 (95% CI 0.72-1.30; p=0.8); the relative risk of progression of disability or entering institutional care was 0.96 (95% CI 0.74-1.24; p=0.7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse events or deaths, or between 5 mg and 10 mg donepezil. INTERPRETATION: Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than cholinesterase inhibitors are needed for Alzheimer's disease.